The overall purpose of the SC Cardiovascular COBRE Gene Function Core Is to provide intellectual and physical resources (specifically transgenic and gene targeted mice) to enhance our understanding of cardiovascular malformations and adult cardiac disease, while supporting all investigators around the state of SC in using genetically modified mice. The renewal proposal of this Core builds upon the previous investments of the NIH/NCRR COBRE Phase I and II programs, NIH/NCRR Shared Instrumentation Grant, NIH/NCRR construction grant, and institutional support. The Gene Function COBRE Core integrates two existing state-of-the-art intramural shared resource facilities each of which are unique within the state of SC: the MUSC Transgenic Facility and the MUSC Gene Targeting Facility. The Gene Function Core also offers plasmid construction, optimizing PCR, genotyping, mentoring PIs, and training lab personnel. Since 2001 the COBRE Gene Function Core has serviced over 50 different investigators and facilitated their research involving >$45 million of extramural grant support. During this time period the Gene Function Core has added new services, like cryopreservation, rederivation, and in vitro fertilization, to facilitate the use and transfer of genetically modified mice. A critical addition has been the ability to make both transgenic and gene targeted mice in the C57BL/6 strain. Since the Gene Function Core provides the only means to make genetically modified mice within the State of South Carolina, this Core will continue to support the research programs of MUSC faculty and throughout the state, as we have over the past 10 years. The major aims of the Gene Function Core during Phase III COBRE funding are: 1) to expand the use of genetically modified mice through consultation and education, 2) to provide the expertise and resources required to design and generate DNA constructs for production of genetically modified mice, 3) to generate new transgenic mice, 4) to generate new gene-targeted mice, 5) to employ business practices and pricing that foster long term sustainability of the core, and 6) to facilitate the mission of the Cardiovascular Developmental Biology Center (CDBC) in understanding the developmental basis of cardiovascular diseases.